Mori Kenichi, Hata Masayuki, Neya Saburo, Hoshino Tyuji
Department of Physical Chemistry, Graduate School of Pharmaceutical Sciences, Chiba University, Inage-ku, Chiba 263-8522, Japan.
J Am Chem Soc. 2005 Nov 2;127(43):15127-37. doi: 10.1021/ja0467972.
A computational study was performed on the Mg(2+)-free conformations of the small guanine nucleotide-binding proteins (GNBPs): Ras, Rho, Rab, Arf, and Ran, which were complexed with GDP. Molecular dynamics (MD) simulation was executed for each complex for the duration of 3.0 ns to investigate the effects of Mg(2+) ions on the GNBPs' structure. The results indicated that all Mg(2+)-free GNBPs formed a groove between the switch region and the nucleotide-binding site. In some GNBP families, the release of Mg(2+) was reported to play an important role in binding the guanine nucleotide-exchanging factor (GEF) promoting the GDP/GTP exchange reaction. Interestingly, the grooves, which appeared in the MD simulations, were similar to the grooves experimentally observed in the GNBP-GEF complex. We also calculated the Mg(2+)-bound GNBPs to compare with the Mg(2+)-free forms. No groove was observed in the Mg(2+)-bound GNBPs. These results demonstrated a regulatory role of Mg(2+) ion to prepare a template for the GEF binding. Moreover, the results suggested that the release of Mg(2+) ion lead to the GEF-GNBP binding.
对与GDP结合的小GTP结合蛋白（GNBPs）：Ras、Rho、Rab、Arf和Ran的无Mg(2+)构象进行了计算研究。对每个复合物进行了3.0 ns的分子动力学（MD）模拟，以研究Mg(2+)离子对GNBPs结构的影响。结果表明，所有无Mg(2+)的GNBPs在开关区域和核苷酸结合位点之间形成了一个凹槽。在一些GNBP家族中，据报道Mg(2+)的释放对结合促进GDP/GTP交换反应的鸟嘌呤核苷酸交换因子（GEF）起着重要作用。有趣的是，MD模拟中出现的凹槽与在GNBP-GEF复合物中实验观察到的凹槽相似。我们还计算了结合Mg(2+)的GNBPs，以与无Mg(2+)形式进行比较。在结合Mg(2+)的GNBPs中未观察到凹槽。这些结果证明了Mg(2+)离子在为GEF结合准备模板方面的调节作用。此外，结果表明Mg(2+)离子的释放导致了GEF-GNBP结合。
